Published April 9, 2020 as 10.3174/ajnr.A6509

ORIGINAL RESEARCH PEDIATRICS

Utility of Pre-Hematopoietic Cell Transplantation Sinus CT Screening in Children and Adolescents

J.H. Harreld, R.A. Kaufman, G. Kang, G. Maron, W. Mitchell, J.W. Thompson, and A. Srinivasan

ABSTRACT BACKGROUND AND PURPOSE: The clinical benefit of pre-hematopoietic cell transplantation sinus CT screening remains uncertain, while the risks of CT radiation and anesthesia are increasingly evident. We sought to re-assess the impact of screening sinus CT on pretransplantation patient management and prediction of posttransplantation invasive fungal rhinosinusitis.

MATERIALS AND METHODS: Pretransplantation noncontrast screening sinus CTs for 100 consecutive patients (mean age, 11.9 6 5.5 years) were graded for mucosal thickening (Lund-Mackay score) and for signs of noninvasive or invasive fungal rhinosinusitis (sinus calcification, hyperattenuation, bone destruction, extrasinus inflammation, and nasal mucosal ulceration). Posttransplantation sinus CTs performed for sinus-related symptoms were similarly graded. Associations of Lund-Mackay scores, clinical assessments, changes in pretransplantation clinical management (additional antibiotic or fungal therapy, sinonasal surgery, delayed transplanta- tion), and subsequent development of sinus-related symptoms or invasive fungal rhinosinusitis were tested (exact Wilcoxon rank sums, Fisher exact test, significance P , .05).

RESULTS: Mean pretransplantation screening Lund-Mackay scores (n ¼ 100) were greater in patients with clinical symptoms (8.07 6 6.00 versus 2.48 6 3.51, P , .001) but were not associated with pretransplantation management changes and did not predict post- transplantation sinus symptoms (n ¼ 21, P ¼ .47) or invasive fungal rhinosinusitis symptoms (n ¼ 2, P ¼ .59).

CONCLUSIONS: Pre-hematopoietic cell transplantation sinus CT does not meaningfully contribute to pretransplantation patient management or prediction of posttransplantation sinus disease, including invasive fungal rhinosinusitis, in children. The risks associ- ated with CT radiation and possible anesthesia are not warranted in this setting.

ABBREVIATIONS: ENT ¼ ear, nose, and throat; GVHD ¼ graft versus host disease; HCT ¼ hematopoietic cell transplantation; IFRS ¼ invasive fungal rhinosinusitis

ue to prolonged immunosuppression, children under- (ENT) examination, infectious disease risk assessment, fungal Dgoing hematopoietic cell transplantation (HCT) are at serologies, and noncontrast sinus CT. increased risk of opportunistic infections, including potentially However, the clinical utility of screening sinus CT remains lethal invasive fungal rhinosinusitis (IFRS).1-5 Children at St. unclear, and the practice is not universal. According to the Jude Children’s Research Hospital, therefore, undergo rigorous American Academy of Pediatrics and the American College of pretransplantation evaluation, including ear, nose, and throat Radiology, uncomplicated sinusitis should be a clinical diagno- sis,6,7 and several large studies (n $ 100) have failed to identify pre-HCT imaging features predictive of post-HCT sinusitis.8-10 Received June 3, 2019; accepted after revision March 3, 2020. From the Departments of Diagnostic Imaging (J.H.H., R.A.K.), Biostatistics Fewer studies have evaluated the contribution of pretransplanta- (G.K.), Infectious Diseases (G.M.), Bone Marrow Transplantation and Cellular tion CT to patient management or prediction of posttransplanta- Therapy (W.M., A.S.), and Surgery (J.W.T.), St. Jude Children’s Research Hospital, Memphis, Tennessee; and Department of Otolaryngology (J.W.T.), University of tion IFRS. A small study in adults found that screening sinus CT Tennessee Health Sciences Center, Memphis, Tennessee. did not contribute to a pretransplantation diagnosis or manage- This work was supported, in part, by grant No. CA21765 from the National Cancer ment or predict posttransplantation sinusitis or IFRS, but it was Institute and by the American Lebanese and Syrian Associated Charities. 11 Please address correspondence to Julie H. Harreld, MD, Department of Diagnostic limited by a small sample size. A study of 187 children reported Imaging, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, MS 220, an association between pre-HCT sinus CT findings and manage- Memphis, TN 38105; e-mail: [email protected] ment changes, but while 119 (64%) had abnormal sinus CT find- Indicates open access to non-subscribers at www.ajnr.org ings, only 29 had symptoms and were treated, suggesting http://dx.doi.org/10.3174/ajnr.A6509 symptoms, not imaging, drove treatment.12

AJNR Am J Neuroradiol :2020 www.ajnr.org 1

Copyright 2020 by American Society of Neuroradiology. While the benefits of pre-HCT sinus CT remain unclear, the Images were reviewed in consensus by a board-certified pe- risks associated with sinus CT are well-established and include diatric radiologist with 40 years’ experience (R.A.K.) and a a low-but-real risk of radiation-induced cancers13,14 and early board-certified neuroradiologist with 10 years’ experience cataract formation.15 Evidence is also emerging that anesthesia, (J.H.H.) for the presence or absence of bone destruction, required by some children to complete CT, may negatively extrasinus inflammation, and nasal mucosal ulceration, associ- impact cognitive development.16,17 On the other hand, advan- ated with IFRS.4,19-22 Because noninvasive fungal disease ces in fungal prophylaxis have significantly reduced the inci- could theoretically predispose to IFRS with pre-HCT condi- dence of invasive fungal infections in immunocompromised tioning/immunodepletion, the presence of calcifications and children.18 sinus hyperdensity was also noted.23 Given these potential shifts in the risk-benefit ratio, we sought Each anterior and posterior ethmoid, maxillary, frontal, and to re-evaluate the clinical utility of pre-HCT screening sinus CT sphenoid sinus was graded as clear ¼ 0, partially opacified ¼ 1, for IFRS risk assessment and its role in pre-HCT management of or completely opacified ¼ 2; each ostiomeatal unit was graded pediatric patients. as clear ¼ 0 or occluded ¼ 2; and the numbers were added per Lund and Mackay.24 To account for age-related differences in MATERIALS AND METHODS sinus development, we calculated an adjusted Lund-Mackay 25 With institutional review board approval and waiver of consent, score as imaging, clinical, ENT risk assessment, and laboratory data were Adjusted Lund Score ¼ prospectively recorded for 100 sequential participants who had pre-HCT screening sinus CT at our institution between June 24 : Raw score : 2015 and April 2017. A sample size of 100 was chosen to detect at Maximum Lund for No Pneumatized Sinuses least 1 case of IFRS, which has an incidence of approximately 2% in patients with hematologic disorders.2 The patients’ medical records were reviewed for microbiologic diagnosis of IFRS for at Statistical Analysis least 100 days posttransplantation. With additional institutional Sinus CT scores, laboratory values, symptoms, changes in man- review board approval and waiver of consent, medical records agement, and ENT risk were compared using the Fisher exact test 2 were retrospectively reviewed for subsequent clinical, imaging, or the Pearson x test for categoric variables and a 2-sample t test and laboratory data until the patient’s death or November 2017. or (exact) Wilcoxon rank sum test for continuous variables, based on the normality assumption. The Lund-Mackay scores between Clinic and Laboratory pre- and posttransplantation were compared using a 1-sample t Recorded data included primary diagnosis; transplant donor test or Wilcoxon signed rank test, depending the normality type; absolute neutrophil count at imaging; pretransplantation assumption. All P values are 2-sided and were considered statisti- imaging indication; development of posttransplantation graft ver- cally significant if ,.05. Statistical analyses were performed with sus host disease (GVHD) grades II–IV (moderate-to-life-threat- R-3.6.1 (R statistical and computing software; http://www.r- ening); pretransplantation galactomannan (Aspergillus antigen); project.org/). sinonasal symptoms (rhinorrhea, congestion, nasal/facial pain, swelling, visible nasal lesion), or fever at pretransplantation evalu- ation; and changes to pretransplantation management (changes RESULTS in fungal prophylaxis regimen, addition of antibiotics, sinonasal One hundred participants (60 males, 40 females; 8 months to 6 6 operation, or delay of HCT) attributable to screening sinus CT. 24 years of age; mean, 11.9 5.5 years; males, 11.6 5.7 years; 6 ENT pretransplantation risk assessment included visualiza- females, 12.5 5.2 years) had screening sinus CT an average of 6 tion of the nasal septum, palate, and back of throat under magni- 24.6 9.6 days before transplantation for IFRS risk assessment. fication and complete allergy and sinusitis histories. These Patient characteristics, imaging, and clinical findings are sum- findings were summarized as “at-risk” or “not at-risk” for IFRS. marized in Table 1. ¼ For patients requiring post-HCT sinus imaging for symptoms, Follow-up for survivors (n 82) ranged from 189 to 889 days we recorded symptoms, galactomannan serologies, endoscopy post-HCT. During the follow-up period, 9 patients died of findings, fungal organism (if applicable), and consecutive days of relapsed disease from 28 to 519 days post-HCT. Nine died of neutropenia (absolute neutrophil count , 500/mm3) immedi- complications between 23 and 557 days post-HCT, none related ately preceding imaging. The date of acquisition of tissue positive to sinus disease. for IFRS by microbiologic/pathologic examination was consid- ered the date of diagnosis. Clinical Symptoms and Provided Imaging Indications At the time of the screening sinus CT, 18 patients had sinonasal Imaging symptoms documented in the medical record: Thirteen had rhin- CTs were axially acquired with a section thickness of #2.5 mm orrhea, 2 had nasal congestion, and 3 had both. No patients had on a LightSpeed VCT or Revolution CT scanner (GE Healthcare) overt signs or symptoms of IFRS or complicated rhinosinusitis— with bone and soft-tissue reconstructions. The average effective localized facial pain or inflammation, nasal ulcer/eschar, fever, or dose for all ages was 0.8 mSv; the eye/lens dose was 0.7–1.2 altered mental status—documented in the medical record at the mGy. time of CT.

2 Harreld 2020 www.ajnr.org The provided indication for 98/100 screening sinus CTs was with antibiotics (5/18 with symptoms versus 0/82 asymptomatic, “pretransplantation evaluation.” Symptoms mentioned for 2 P ¼ .0001). The Lund-Mackay scores were greater for sympto- patients did not match the medical record, possibly being errone- matic patients who received antibiotics (n ¼ 5, 12.8 6 5.72) com- ous or outdated. One request indicated fever without localizing pared with those who did not (n ¼ 13, 6.25 6 5.25), but this symptoms, though the clinical examination documented conges- finding did not reach statistical significance (P ¼ .058) (Table 2). tion and rhinorrhea without fever. The other request indicated All 5 patients treated with pretransplantation antibiotics had possible periorbital edema, which was not present on CT or the clinical sinusitis. Nasal wash was positive for enterovirus/rhinovi- physical examination. On examination, the patient had clear rus in 3/5 (60%). Two received antibiotics primarily for pneumo- rhinorrhea and nasal wash positive for enterovirus/rhinovirus nia and secondary coverage of possible bacterial sinusitis. None and was determined eligible for transplantation the same day. developed IFRS before or after transplantation. One patient had a smooth nasal septal perforation, which was negative for IFRS at screening endoscopy. Two others had sinus Pretransplantation Screening and Management calcifications. All 3 were asymptomatic, and none developed Mucosal thickening was present (Lund-Mackay score of $1) at IFRS or symptoms posttransplantation. No patients (0/100) had screening in 66/100 patients, including 48/82 (58.5%) asymptom- sinus hyperdensity, nasal ulceration, extrasinus inflammation, or atic patients and all 18 symptomatic patients. No asymptomatic bone destruction at screening. patients received antibiotics based on sinus CT. No patients underwent a pretransplantation sinus operation, The Lund-Mackay score was higher for patients with symp- received new antifungal therapy, or had HCT delayed as a result toms documented in the medical record (P , .0001, Table 2). of screening sinus CT. Patients with clinical symptoms were more likely to be treated Posttransplantation Imaging Table 1: Patient characteristics Symptoms prompted posttransplantation evaluation of 21 Characteristics patients whose Lund-Mackay scores had increased (7.43 6 6.36) No. 100 from baseline screening CT (3.87 6 4.99; P ¼ .007). Male 60 Female 40 Two of the 21 (9.5%) symptomatic patients or 2% (2/100) of the Age (mean) (yr) 11.9 6 5.5 entire cohort developed IFRS, 615 days (Bipolaris spp) and 248 days Primary diagnosis (No.) (%) (Fusarium spp) posttransplantation. Pretransplantation, neither had Hematologic malignancy 65, 65% symptoms. These 2 patients had lower Lund-Mackay scores (4.5 6 Acute myeloid leukemia 34, 34% 3.54) than symptomatic patients without IFRS (n ¼ 19, 7.74 6 Acute lymphoblastic leukemia 17, 17% ¼ Hodgkin lymphoma 8, 8% 6.57), but this finding was not statistically significant (P .59). Myelodysplastic syndrome 5, 5% Anaplastic large-cell lymphoma 1, 1% Prediction of Posttransplantation Sinus Disease Hematologic disorder 5, 5% The degree of mucosal thickening (Lund-Mackay score) on pre- Severe aplastic anemia 3, 3% transplantation CT did not predict posttransplantation symptoms Sickle cell disease 2, 2% (P ¼ .47) or posttransplantation IFRS (P ¼ .58) (Table 3). Solid tumor 28, 28% Neuroblastoma 15, 15% The pretransplantation test for galactomannan was negative in Ewing sarcoma 9, 9% all patients at screening. The mean absolute neutrophil count at Germ cell tumor 3, 3% screening was 2510 6 5568 (range, 0–50,200). There was no asso- Desmoplastic small round cell tumor 1, 1% ciation between screening absolute neutrophil count and pre-HCT Immune disorder 2, 2% symptoms, post-HCT symptoms, or post-HCT IFRS. Disease sta- Severe combined immunodeficiency 1. 1% Wiskott-Aldrich syndrome 1, 1% tus, transplant donor, T-cell depletion, and posttransplantation Transplant donor (No.) (%) GVHD grades II–IV did not predict development of IFRS (P ¼ 1 Allogenic 66, 66% for all; Table 4). Autologous 34, 34% Of 96 participants evaluated by ENT, 29 were considered at Disease status at transplantation (No.) (%) Complete remission 82, 82% risk for IFRS. ENT risk assessment did not predict development Active disease 18, 18% of IFRS (P ¼ .61). There was no association between the Lund- T-cell depletion (No.) (%) 2, 2% Mackay score and the ENT risk stratum (P ¼ .99). GVHD II–IV (No.) (%) 15, 15% The presence of symptoms before transplantation (n = 18) did not predict posttransplantation symp- Table 2: Pretransplantation sinus CT Lund-Mackay scores, sinonasal symptoms, and toms (n ¼ 21); only 3 patients were management symptomatic both before and after Pre-HCT Lund-Mackay transplantation (P ¼ .62). No. (Frequency) Score (Mean) P Value All at screening 100 (100%) 3.48 6 4.58 No symptoms at screening 82 (82%) 2.48 6 3.51 ,.001 DISCUSSION Symptoms at screening 18 (18%) 8.07 6 6.00 In this study, we found no association With symptoms, received antibiotics 5 (28%) 12.80 6 5.72 .058 between pre-HCT screening sinus 6 With symptoms, no antibiotics 13 (72%) 6.25 5.25 CT and changes in pretransplantation

AJNR Am J Neuroradiol :2020 www.ajnr.org 3 Table 3: Pre-HCT Lund-Mackay scores versus posttransplantation sinus outcomes in 2000, Billings et al29 found that chil- Pre-HCT Lund-Mackay dren with severe sinus disease on pre- No. (Frequency) Score (Mean) P Value bone marrow transplantation CT were All at screening 100 (100%) 3.48 6 4.58 more likely to have sinusitis after bone 6 No post-HCT symptoms 79 (79%) 3.38 4.49 .47 marrow transplantation and reported Post-HCT symptoms 21 (21%) 3.86 6 5.00 Post-HCT symptoms, IFRS 2 (9.5%) 4.00 6 4.24 .58 a trend toward decreased survival in Post-HCT symptoms, no IFRS 19 (90.5%) 3.84 6 5.17 these children, but these findings were not statistically significant (P ¼ .750). In a study of 252 adults, Won et al9 Table 4: Clinical findings at screening for patients who did and did not develop IFRS found that asymptomatic radiographic after transplantation sinus abnormalities did not increase All at Pre-HCT No Post- Post-HCT P Screen HCT IFRS IFRS Value the risk of post-HCT sinusitis, but they also reported a trend toward reduction No. 100 98 2 ENT risk estimate (No.) (frequency) of post-HCT sinusitis with the treat- At risk 29 (29%) 28 (29%) 1 (50%) .61 ment of asymptomatic abnormalities, Low risk 67 (67%) 62 (63%) 1 (50%) which did not reach statistical signifi- Not evaluated 4 (4%) 8 (8%) 0 cance (P ¼ .057). To our knowledge, ANC at imaging (mean) 2510 6 5568 2524 6 5622 1800 6 1697 .86 Transplant donor (No.) (frequency) no investigators have identified pre- Allogenic 66 (66%) 65 (66%) 1 (50%) 1 transplantation imaging predictors of Autologous 34 (34%) 33 (34%) 1 (50%) IFRS. Disease status at transplantation It has been suggested that CT (No.) (frequency) might be a surrogate for inflammatory Complete remission 82 (82%) 80 (80%) 2 (100%) 1 Active disease 18 (18%) 18 (18%) symptoms in immunocompromised T-cell depletion (No.) (frequency) 2 (2%) 2 (2%) 0 1 patients, who may not be able to GVHD II–IV (No.) (frequency) 15 (15%) 15 (15%) 0 1 mount an inflammatory response.27,30 Note:—ANC indicates absolute neutrophil count. However, evidence shows that clinical sinusitis and imaging severity go hand in hand, even in immunocompro- patient management, including the addition of antibiotics or mised children.10,29,30 This was also true in our study, in which changes to the antifungal prophylaxis regimen or transplantation Lund-Mackay scores were greater in the presence of symptoms. schedule. Like other authors,9,10 we found no association between The American Academy of Pediatrics and American College of pretransplantation Lund-Mackay scores and the development of Radiology guidelines dictate that diagnosis and treatment of acute posttransplantation sinus symptoms or IFRS. Unlike Won et al,9 sinusitis should be clinical, with imaging reserved for suspicion of we did not find pre-HCT symptoms predictive of post-HCT orbital or CNS complications.6,7 IFRS typically presents with a symptoms. In our study, clinical and laboratory features, includ- combination of fever, facial pain, nasal congestion, headache, eye ing pretransplantation ENT evaluation, also failed to predict post- symptoms, and/or facial swelling, which should also prompt transplantation sinusitis and IFRS. Our findings are in agreement imaging, and likely endoscopy.3-5,31 On pretransplantation physi- with adult studies by Thompson et al8 (n ¼ 100) and Moeller cal examination, none of the 100 patients in our series had find- et al11 (n ¼ 71), which found no benefit at all for pre-HCT sinus ings suggestive of orbital, CNS, or fungal involvement warranting screening. A similar study of 1589 adult patients with kidney imaging evaluation. transplants found no increase in the prevalence of rhinosinusitis On the other hand, isolated radiographic abnormalities, posttransplantation, concluding that routine pretransplantation common in asymptomatic children,32 may be confusing or sinonasal evaluation is not warranted.26 lead to overtreatment.33 In our series, 58.8% of 82 asymptom- The origins and evidence supporting pre-HCT screening atic children had mucosal thickening on pre-HCT CT. As sug- sinus CT are unclear. In a 1995 study, Shibuya et al27 recom- gested by other authors,9,30 a thorough sinus history and mended screening CT on the basis of 33/107 pretransplantation examination are likely to be more meaningful than CT, with- patients with clinical sinusitis and imaging abnormalities, despite out the associated risk of radiation-induced cancers and cata- imaging only symptomatic patients. At our institution, the prac- racts.13-15,34 tice may date back to a 1982 article by Bartley et al,28 prompting Our findings suggest that there is insufficient benefit to justify routine screening abdominal CT for detection of hepatosplenic the risks of radiation exposure, and potentially of anesthesia, fungal abscesses, to which chest and sinus CT were subsequently associated with pre-HCT screening CT.13,15-17 To reduce the risk added. Subsequent work by Kasow et al12 found no utility in rou- of radiation-induced cancers, to which children are particularly tine chest or abdominal CT in asymptomatic patients but sug- susceptible,34 the As Low As Reasonably Achievable principle gested that sinus CT drove changes in management. However, dictates the use of the lowest possible radiation dose necessary supporting data were sparse, and the number of treated and for diagnosis.34 Most pediatric imaging centers, like ours, use symptomatic patients precisely matched (n ¼ 29/187, 15.5%), targeted protocols with dose-reduction techniques like itera- suggesting a clinical basis for treatment. In a small (n ¼ 51) study tive reconstruction and low tube voltage wherever possible.35

4 Harreld 2020 www.ajnr.org However, the best way to reduce the pediatric radiation dose is 2. Chen CY, Sheng WH, Cheng A, et al. Invasive fungal sinusitis in to eliminate imaging that does not meaningfully contribute to patients with hematological malignancy: 15 years’ experience in a diagnosis or management.14 Thepreponderanceoftheevi- single university hospital in Taiwan. BMC Infect Dis 2011;11:250 CrossRef Medline dence, including ours, suggests that pre-HCT screening sinus 3. Gillespie MB, O’Malley BW, Francis HW. An approach to fulminant CT falls into this category andthatthepracticeshouldbe invasive fungal rhinosinusitis in the immunocompromised host. discontinued. Arch Otolaryngol Head Neck Surg 1998;124:520–26 CrossRef Medline This study had several weaknesses. Clinical evaluation was 4. Park AH, Muntz HR, Smith ME, et al. Pediatric invasive fungal rhino- rarely performed on the same day as screening sinus CT, and sinusitis in immunocompromised children with cancer. Otolaryngol Head Neck Surg 2005;133:411–16 CrossRef Medline symptoms were recorded from the medical record because they 5. Smith A, Thimmappa V, Shepherd B, et al. Invasive fungal sinusitis were frequently omitted from the imaging requisitions. These fea- in the pediatric population: systematic review with quantitative syn- tures could result in a mismatch between symptoms and imaging thesis of the literature. Int J Pediatr Otorhinolaryngol 2016;90:231–35 manifestations. Although a trend toward greater Lund-Mackay CrossRef Medline scores in symptomatic patients receiving antibiotics was not statis- 6. Kirsch CF, Bykowski J, Aulino JM, et al; Expert Panel on Neurologic Imaging. ACR Appropriateness Criteria Sinonasal Disease. JAm tically significant, the sample size was small. It is possible that the Coll Radiology 2017;14:S550–59 CrossRef Medline degree of mucosal thickening on sinus CT unduly influenced the 7. Wald ER, Applegate KE, Bordley C, et al; American Academy of decision to treat with antibiotics, which should be based on history Pediatrics. Clinical practice guideline for the diagnosis and man- and examination.6,7 Mucosal thickening on CT does not differenti- agement of acute bacterial sinusitis in children aged 1 to 18 years. – ate between bacterial and viral pathogens, and 3 of 5 patients Pediatrics 2013;132:e262 80 CrossRef Medline 8. Thompson AM, Couch M, Zahurak ML, et al. Risk factors for post- receiving antibiotics in this study had nasal washes positive for vi- stem cell transplant sinusitis. Bone Marrow Transplant 2002;29:257– ral pathogens. Next, only patients undergoing imaging work-up 61 CrossRef Medline were considered symptomatic post-HCT. It is possible that some 9. Won YW, Yi SY, Jang JH, et al. Retrospective analysis of paranasal patients were treated on the basis of clinical symptoms with no sinusitis in patients receiving hematopoietic stem cell transplanta- – imaging, though observation of our current clinical practice sug- tion. Int J Hematol 2011;93:383 88 CrossRef Medline 2,4 10. Zamora CA, Oppenheimer AG, Dave H, et al. The role of screening gests that this is unlikely. Similar to other studies, only 2% (2/ sinus computed tomography in pediatric hematopoietic stem cell 100) of this study population ultimately developed IFRS, limiting transplant patients. J Comput Assist Tomogr 2015;39:228–31 CrossRef statistical evaluation. However, neither had clinical or imaging Medline findings suspicious for IFRS pretransplantation. Although a single- 11. Moeller CW, Martin J, Welch KC. Sinonasal evaluation preceding he- – institution sample size of 100 children undergoing HCT may be matopoietic transplantation. Otolaryngol Head Neck Surg 2011;144:796 801 CrossRef Medline considered large, given the rarity of the condition, it was nonethe- 12. Kasow KA, Krueger J, Srivastava DK, et al. Clinical utility of com- less insufficient to identify clinical or imaging features associated puted tomography screening of chest, abdomen, and sinuses before with IFRS. A retrospective case-control study would be more prac- hematopoietic stem cell transplantation: the St. Jude experience. Biol tical for such analysis. Blood Marrow Transplant 2009;15:490–95 CrossRef Medline 13. Miglioretti DL, Johnson E, Williams A, et al. The use of computed tomography in pediatrics and the associated radiation exposure CONCLUSIONS and estimated cancer risk. JAMA Pediatr 2013;167:700–07 CrossRef Medline Pre-HCT sinus CT does not meaningfully contribute to pretrans- 14. Donnelly LF. Reducing radiation dose associated with pediatric plantation patient management or prediction of posttransplanta- CT by decreasing unnecessary examinations. AJR Am J Roentgenol tion sinus disease, including IFRS, in children. The risks associated 2005;184:655–57 CrossRef Medline with CT radiation and possible anesthesia are not warranted in this 15. Fish DE, Kim A, Ornelas C, et al. The risk of radiation exposure to setting. the eyes of the interventional pain physician. Radiology Res Pract 2011;2011:609537 CrossRef Medline 16. Banerjee P, Rossi MG, Anghelescu DL, et al. Association between an- ACKNOWLEDGMENTS esthesia exposure and neurocognitive and neuroimaging outcomes The authors wish to thank Edwina Anderson and Cindy Morris in long-term survivors of childhood acute lymphoblastic leukemia. for assistance with data collection. JAMA Oncol 2019 Jun 20. [Epub ahead of print] CrossRef Medline 17. Lei S, Ko R, Sun LS. Neurocognitive impact of anesthesia in chil- dren. Adv Anesth 2018;36:125–37 CrossRef Medline Disclosures: Julie H. Harreld—RELATED: Grant: National Cancer Institute, 18. Maron GM, Hayden RT, Rodriguez A, et al. Voriconazole prophy- Comments Other : Grant No. CA21765 supports the St. Jude Cancer Center*; : laxis in children with cancer: changing outcomes and epidemiology American Lebanese and Syrian Associated Charities, Comments: The American of fungal infections. Pediatr Infect Dis J 2013;32:e451–55 CrossRef Lebanese and Syrian Associated Charities is the fundraising arm of St. Jude.* Gabriela Maron—UNRELATED: Other: Astellas Pharma Inc, Comments: local Medline Principal Investigator for pharmaceutical research protocols.* Jerome W. 19. DelGaudio JM, Swain RE Jr, Kingdom TT, et al. Computed tomo- Thompson—UNRELATED: Employment: University of Tennessee Faculty. *Money graphic findings in patients with invasive fungal sinusitis. Arch paid to the institution. Otolaryngol Head Neck Surg 2003;129:236–40 CrossRef Medline 20. 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